Thermal flow meter

ABSTRACT

A flow meter for use in dialysis is described, that uses a thermal wave to generate a signal in the fluid for which the flow rate is to be measured. The phase angle of the thermal wave signal changes when traversing downstream. The phase difference between the signals received downstream, compared with a reference excitation source signal is measured, and used to determine the flow rate of the fluid.

CROSS-REFERENCE

The present application is a continuation of U.S. patent applicationSer. No. 12/575,449, filed on Oct. 7, 2009, which relies upon U.S.Patent Provisional Application No. 61/103,271, filed on Oct. 7, 2008,for priority and which is a continuation-in-part of U.S. patentapplication Ser. No. 12/249,090, filed on Oct. 10, 2008, which relies onU.S. Patent Provisional Application No. 60/979,113, filed on Oct. 11,2007, for priority. All of the aforementioned applications are hereinincorporated by reference.

FIELD OF THE INVENTION

The present invention generally relates to the field of systems andmethods for fluid flow rate measurement, and, more specifically, to athermal fluid flow meter for use in a dialysis manifold system.

BACKGROUND OF THE INVENTION

Fluid flow meters operate based upon the principle that the propagationvelocity of a wave in a fluid, as determined by measuring the phaseshift of the signal, is indicative of the velocity of the fluid. U.S.Pat. No. 3,894,431 to Muston, et al discloses determining fluid flowrates “by transmitting ultrasonic pulses in both directions along a paththrough the fluid aligned with the direction in which velocity componentis to be measured. Transmission of, and measurement upon, pulses in thetwo directions are controlled by a master clock pulse generator. Thefrequency of a first variable frequency oscillator is adjusted to fit Npulses exactly into the timer period for flight of an ultrasonic pulsealong the path in one direction. The frequency of a second variablefrequency oscillator is adjusted to fit N pulses exactly into the timeperiod for flight of an ultrasonic pulse along the path in the oppositedirection. The difference frequency is proportional to velocitycomponent. This system may be combined with a limited sing-around systemto improve resolution, at the expense of the time response.”

U.S. Pat. No. 4,885,942 to Magori discloses using “the phase differencemethod wherein two ultrasound transducers W1 and W2 are mounted offsetbut aligned with each other in a tube through which the velocity of flowis to be measured wherein both of the ultrasound transducers are excitedin a pulse manner by an oscillator OS2 and wherein receiving amplifiersV1 and V2 are, respectively, associated with the ultrasound transducersW1 and W2. Evaluation devices are connected after amplifier V1 and V2such that the phase relationship of the signals at the outputs of thereceiving amplifiers V1 and V2 is determined during the reception ofultrasound signals. The phase relationship between the signals at theultrasound transducers is also determined during transmission ofultrasound signals and this phase difference is used as a referenceduring reception of ultrasound signals.”

U.S. Patent Publication No. 2006/0106308 describes use of thermalmeasurements to detect and/or measure the reestablishment of blood flowduring a clot dissolution treatment. A catheter 10 is positioned througha clot 90 at a treatment site 88 in a patient's vasculature 86. Thecatheter 10 includes at least an upstream thermal source 120 and adownstream thermal detector 122. When the thermal source 120 suppliesthermal energy into the surrounding environment, a “thermal pulse” 124is created therein. As the thermal pulse 124 propagates downstream, thecharacteristics of the thermal pulse 124 will change, which can bemeasured and analyzed using the thermal detector, thereby providinginformation about blood flow at the treatment site.

U.S. Patent Publication No. 2003/0056585 describes a thermal flow meterwith a flow rate detecting unit containing a heating element, a flowrate detecting temperature sensing element and a flow rate detectingelectroconductive heat transfer member extending into a fluid flowpassage, which are disposed so as to enable heat transfer therebetween,the flow rate detecting temperature sensing element varying inelectrical characteristic value in accordance with flow of a fluid inthe fluid flow passage through heat exchange with the fluid in the fluidflow passage which is carried out through the flow rate detectingelectroconductive heat transfer member; and a fluid temperaturedetecting unit containing a fluid temperature detecting temperaturesensing element and a fluid temperature detecting electroconductive heattransfer member extending into the fluid flow passage, which aredisposed so as to enable heat transfer therebetween, the fluidtemperature detecting temperature sensing element varying in electricalcharacteristic value in accordance with the temperature of the fluidthrough heat exchange with the fluid in the fluid flow passage, whereina flow rate of the fluid is detected on the basis of the electricalcharacteristic value of the flow rate detecting temperature sensingelement and the electrical characteristic value of the fluid temperaturedetecting temperature sensing element, and fluid discrimination iseffected by determining a conductivity between the flow rate detectingelectroconductive heat transfer member and the fluid temperaturedetecting electroconductive heat transfer member. All of theaforementioned patents and published applications are hereinincorporated by reference.

These aforementioned prior art flow meters often suffer from excessivenoise and may have limited efficacy where space around the flowing fluidis limited (such as in conduits of small diameters). These conditionsare typically true for medical applications and are particularly so inextracorporeal blood processing systems such as hemodialysis,hemofiltration and hemodiafiltration systems.

Accordingly, there is need in the art for a thermal flow meter that hasimproved accuracy and efficiacy. There is also a need in the art for athermal flow meter that has decreased sensitivity to noise and signaldispersion. Finally, there is a need in the art for a thermal flow meterthat can be readily implemented in a manifold, does not requireexpensive, non-disposable materials, and can generate a signal that canbe readily, and easily, filtered.

SUMMARY OF THE INVENTION

In one embodiment, the present invention is directed toward a flow ratesensor for sensing the flow rate of a fluid passing through a channel,comprising a) an excitation probe having a body and a contact surface,wherein said excitation probe is physically positioned within saidchannel; b) a receiver probe having a body and a contact surface,wherein said receiver probe is physically positioned within said channeland wherein said receiver probe senses a thermal wave within said fluid;c) a reference signal generator, wherein said reference signal generatoroutputs a reference signal; d) a heat source, wherein said heat sourcereceives said reference signal from said reference signal generator, isconfigured to thermally engage with said excitation probe, and generatesa first thermal signal, having a frequency derived from said referencesignal; e) a temperature sensor, wherein said temperature sensor isconfigured to thermally engage with said receiver probe, and generates asecond thermal signal, having a frequency derived from said thermalwave; f) a multiplier for receiving an input signal from said referencesignal generator and for receiving said second thermal signal and foroutputting a third signal; and g) a low pass filter for receiving afourth signal, wherein said fourth signal is a function of the thirdsignal, and for receiving an input signal from said reference signalgenerator, wherein said low pass filter modulates its cutoff frequencybased upon the input signal from said reference signal generator.

Optionally, the receiver probe is separated from said excitation probeby a distance of less than two inches. The flow rate sensor furthercomprises an amplifier for amplifying said third signal and generatingsaid fourth signal. The channel area is in the range of 3 mm² to 65 mm².The body of said receiver probe or excitation probe has a diameter inthe range of 0.03 inches to 0.15 inches. The contact surface of saidreceiver probe or excitation probe has a diameter in the range of 0.025inches to 0.2 inches. The excitation probe and receiver probe areembedded into a manifold and wherein the contact surfaces of saidreceiver probe or excitation probe are externally exposed. The receiverprobe comprises a thermistor. The flow rate sensor has an operativesensing range between 20 mL/min to 600 mL/min. The low pass filtergenerates a filtered signal and wherein the reference signal generatorgenerates said reference signal based, at least in part, on saidfiltered signal. The flow rate sensor dynamically adjusts said referencesignal in order to maintain a constant phase.

In another embodiment, the present invention is directed toward amanifold comprising a flow rate sensor for sensing the flow rate of afluid passing through a channel having a hydraulic diameter in a rangeof 1.5 mm to 7.22 mm, comprising a) at least two probes, each having abody embedded into a first surface of said manifold and within saidchannel and each having a contact surface positioned on a surface ofsaid manifold, wherein a second of said at least two probes senses athermal wave within said fluid; b) a reference signal generator, whereinsaid reference signal generator outputs a reference signal; c) a heatsource, wherein said heat source receives said reference signal fromsaid reference signal generator, is configured to thermally engage witha first of said at least two probes, and generates a first thermalsignal, having a phase derived from said reference signal; d) atemperature sensor, wherein said temperature sensor is configured tothermally engage with said second probe, and generates a second thermalsignal, having a phase derived from said thermal wave; e) a multiplierfor receiving an input signal from said reference signal generator andfor receiving said second thermal signal and for outputting a thirdsignal; and f) a low pass filter for receiving a fourth signal, whereinsaid fourth signal is a function of the third signal, and for receivingan input signal from said reference signal generator, wherein said lowpass filter modulates its cutoff frequency based upon the input signalfrom said reference signal generator.

Optionally, the second probe is separated from said excitation probe bya distance of less than two inches. The manifold further comprises anamplifier for amplifying said third signal and generating said fourthsignal. The body of each of said at least two probes has a diameter inthe range of 0.03 inches to 0.15 inches. The contact surface of each ofsaid at least two probes has a diameter in the range of 0.025 inches to0.2 inches. The second probe comprises a thermistor. The low pass filtergenerates a filtered signal and wherein the reference signal generatorgenerates said reference signal based, at least in part, on saidfiltered signal. The flow rate sensor dynamically adjusts said referencesignal in order to maintain a constant frequency. The flow rate sensordynamically adjusts said reference signal in order to maintain aconstant phase.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other features and advantages of the present invention will beappreciated, as they become better understood by reference to thefollowing detailed description when considered in connection with theaccompanying drawings, wherein:

FIG. 1 is a diagram of a dialysis circuit with a flow rate sensor of thepresent invention included therein;

FIG. 2 is a schematic depicting a manifold with a flow rate sensor ofthe present invention included therein;

FIG. 3 provides a perspective view of the thermal flow sensor of thepresent invention integrated into the compact manifold;

FIG. 4 illustrates the installation of the thermal flow sensor alongwith the compact manifold in a dialysis machine;

FIG. 5 a is a top view schematic of one embodiment of the thermal flowmeter of the present invention;

FIG. 5 b is a side view schematic of one embodiment of the thermal flowmeter of the present invention;

FIG. 5 c is an end view schematic of one embodiment of the thermal flowmeter of the present invention;

FIG. 6 a illustrates a schematic for the operation of a thermal flowmeter of the present invention;

FIG. 6 b depicts the relative phases of the thermal wave based on theplacement of a contact and downstream detectors;

FIG. 7 a is a table illustrating the range of excitation frequency thatis dynamically adjusted to maintain a constant phase shift;

FIG. 7 b illustrates the output of the phase sensitive detector for thevalues specified in FIG. 7 a;

FIG. 8 a illustrates a table detailing values of various parameters whenthe excitation frequency is maintained constant;

FIG. 8 b illustrates two sets of outputs for the range of valuesspecified in FIG. 8 a of the phase sensitive detector;

FIG. 8 c illustrates two sets of outputs for the range of valuesspecified in FIG. 8 a of the phase sensitive detector;

FIG. 9 illustrates a table delineating an exemplary set of optimizeddesign parameters;

FIG. 10 is a table illustrating another set of exemplary designparameters for the excitation and receiver probes;

FIG. 11 is a schematic of one embodiment of the present inventionemploying a constant phase mode of operation;

FIG. 12 is a schematic of one embodiment of the present inventionemploying a constant frequency mode of operation; and

FIG. 13 is a graph of signals generated in a constant frequency mode ofoperation.

DETAILED DESCRIPTION OF THE INVENTION

While the present invention may be embodied in many different forms, forthe purpose of understanding of the principles of the invention,reference will now be made to the embodiments illustrated in thedrawings and specific language will be used to describe the same. Itwill nevertheless be understood that no limitation of the scope of theinvention is thereby intended. Any alterations and further modificationsin the described embodiments, and any further applications of theprinciples of the invention as described herein are contemplated aswould normally occur to one skilled in the art to which the inventionrelates.

“Treat,” “treatment,” and variations thereof refer to any reduction inthe extent, frequency, or severity of one or more symptoms or signsassociated with a condition.

“Duration” and variations thereof refer to the time course of aprescribed treatment, from initiation to conclusion, whether thetreatment is concluded because the condition is resolved or thetreatment is suspended for any reason. Over the duration of treatment, aplurality of treatment periods may be prescribed during which one ormore prescribed stimuli are administered to the subject.

“Period” refers to the time over which a “dose” of stimulation isadministered to a subject as part of the prescribe treatment plan.

The term “and/or” means one or all of the listed elements or acombination of any two or more of the listed elements.

The terms “comprises” and variations thereof do not have a limitingmeaning where these terms appear in the description and claims.

Unless otherwise specified, “a,” “an,” “the,” “one or more,” and “atleast one” are used interchangeably and mean one or more than one.

For any method disclosed herein that includes discrete steps, the stepsmay be conducted in any feasible order. And, as appropriate, anycombination of two or more steps may be conducted simultaneously.

Also herein, the recitations of numerical ranges by endpoints includeall numbers subsumed within that range (e.g., 1 to 5 includes 1, 1.5, 2,2.75, 3, 3.80, 4, 5, etc.). Unless otherwise indicated, all numbersexpressing quantities of components, molecular weights, and so forthused in the specification and claims are to be understood as beingmodified in all instances by the term “about.” Accordingly, unlessotherwise indicated to the contrary, the numerical parameters set forthin the specification and claims are approximations that may varydepending upon the desired properties sought to be obtained by thepresent invention. At the very least, and not as an attempt to limit thedoctrine of equivalents to the scope of the claims, each numericalparameter should at least be construed in light of the number ofreported significant digits and by applying ordinary roundingtechniques.

Notwithstanding that the numerical ranges and parameters setting forththe broad scope of the invention are approximations, the numericalvalues set forth in the specific examples are reported as precisely aspossible. All numerical values, however, inherently contain a rangenecessarily resulting from the standard deviation found in theirrespective testing measurements.

The present invention is a flow meter which can be used or implementedin any fluidic channel, tube, cell, passage, or opening. Such channelsinclude: tubing in medical devices, manifolds in medical devices, andother industrial or commercial applications. The present invention isparticularly well suited to sensing temperature levels and changes inapplications where the fluid flow rate is between 10 mL/min to 1000mL/min, particularly 20 mL/min to 600 mL/min. Additionally, the presentinvention is particularly well suited to sensing temperature levels andchanges in applications where the flow can be generally characterized aslaminar, as opposed to turbulent flow. Additionally, the presentinvention is particularly well suited to sensing temperature levels andchanges in applications where the fluid involved has a density in therange of 800 to 1200 kg/m³, and more preferably 1000 kg/m³, a dynamicviscosity in the range of 0.001 kg/(m*s), and/or a kinematic viscosityin the range of 1.002×10-6 m²/s. Finally, the present invention isparticularly well suited to sensing temperature levels and changes inapplications where the fluid flow can be characterized with a Reynoldsnumber in the range of 50 to 2500. Below, the present invention isspecifically described in relation to use in dialysis machines, portabledialysis machines, extracorporeal blood circuits, and disposablemanifolds.

The present invention is a novel thermal signal based flow meter thathas the ability to generate a thermal signal directly in the fluid to bemonitored. The flow meter of the present invention provides flowmeasurement with improved accuracy, and reduced susceptibility to noisegenerated by signal dispersion in prior art implementations. It isfurther contemplated the present flow meter can be incorporated into thestructure of a disposable manifold used in medical applications,particularly dialysis machines. In particular, the present flow metercan be incorporated into the manifold structures and devices disclosedin U.S. patent application Ser. No. 12/237,914, entitled Manifolds forUse in Conducting Dialysis and filed on Sep. 25, 2008, and U.S. patentapplication Ser. No. 12/245,397, entitled Wearable Dialysis Methods andDevices and filed on Oct. 3, 2008, which are incorporated herein byreference in their entirety.

FIG. 1 shows the fluidic circuit for an extracorporeal blood processingsystem 100, used for conducting hemodialysis and hemofiltration.Referring to FIG. 1, the hemodialysis system comprises two circuits—aBlood Circuit 101 and a Dialysate Circuit 102. In one embodiment, thefluid circuits 101 and 102 are implemented in a manifold that can beused with a portable dialysis machine.

For dialysis, the patient's blood is circulated in the blood circuit 101on one side of a semi permeable membrane (dialyzer) 103 and a dialysisliquid called the dialysate, comprising the main electrolytes of theblood in concentrations close to those in the blood of a healthysubject, is circulated on the other side in the dialysate circuit 102.The line 104 from the patient which feeds blood to the dialyzer 103 inthe blood circuit 101 is provided with an occlusion detector 105 whichis generally linked to a visual or audible alarm (not shown) to signalany obstruction to the blood flow. In order to prevent coagulation ofblood, means 106 for injecting an anticoagulant—such as heparin, intothe blood are also provided. A peristaltic pump 107 is also provided toensure flow of blood in the normal (desired) direction.

A pressure sensor 108 is provided at the inlet where impure blood entersthe dialyzer 103. Other pressure sensors 109, 110, 111 and 112 areprovided at various positions in the hemodialysis system that help keeptrack of and maintain fluid pressure at vantage points. Also provided atthe dialyzer input is the thermal flow rate sensor 150 of the presentinvention. The flow rate sensor, in one embodiment, comprises aplurality of contacts which help in generating a thermal signal in thefluid for flow measurement.

At the point where used dialysate fluid from the dialyzer 103 enters thedialysate circuit 102, a blood leak sensor 113 is provided to sense andprevent any leakage of blood into the dialysate circuit. A pair ofbypass valves 114 is also provided at the beginning and end points ofthe dialysate circuit, which ensure that fluid flow is in the desireddirection in the closed loop circuit. Another bypass valve 115 isprovided just before a priming/drain port 116. The port 116 is used forinitially preparing the circuit curves with a priming solution, and toremove used dialysate fluid during dialysis and replace portions ofdialysate with replenishment fluid of appropriate sodium concentration.

The dialysate circuit is provided with two peristaltic pumps 117 and118. Pump 117 is used for pumping out used dialysate fluid to the drainor waste container, as well as for pumping regenerated dialysate intothe dialyzer 103. Pump 118 is used for pumping out spent dialysate fromthe dialyzer 103, and also for pumping in the replacement fluid fromport 116 for maintaining sodium concentration in the dialysate.

A sorbent type cartridge 119 is provided in the dialysate circuit, whichcontains several layers of materials, each having a specific role inremoving impurities such as urea. The combination of these materialsallows water suitable for drinking to be charged into the system for useas dialysate fluid. For the fresh dialysate fluid, a lined container orreservoir 120 of a suitable capacity is provided.

Depending upon patient requirement, desired quantities of an infusatesolution 121 may be added to the dialysis fluid. A peristaltic pump 122is provided to pump the desired amount of infusate solution to thecontainer 120. A camera 123 may optionally be provided to monitor theinflow of the infusate solution.

A heater 124 is provided to maintain the temperature of dialysate fluidin the container 120 at the required level. The temperature of thedialysate fluid can be sensed by the temperature sensor 125. Thecontainer 120 is also equipped with a scale 126 for keeping track of theweight of the fluid in the container, and a conductivity meter 127,which displays the conductivity of the dialysate fluid measured by theconductivity sensor 128. The conductivity sensor 128 provides anindication of the level of sodium in the dialysate.

A medical port 129 is provided before blood from the patient enters thesystem for dialysis. Another medical port 130 is provided before cleanblood from the dialyzer is returned to the patient. An AIL sensor 131and a pinch clamp 132 are employed in the circuit to ensure a smooth andunobstructed flow of clean blood to the patient. Priming sets 133pre-attached is to the hemodialysis system that helps prepare the systembefore it is used for dialysis.

FIG. 2 is an illustration of one embodiment of a hemofiltration circuit.In one embodiment, as further discussed below in FIG. 3, thehemofiltration circuit comprises the blood 211 and dialysate 212 flowpaths that are molded in a single compact plastic unit. All the sensors,including the thermal flow meter 250 of the present invention, thedialyzer blood inlet pressure transducer 203, the blood outlet pressuretransducer 204, conductivity meters 221, 222, and leak sensor 223 areall integrated into the molding of the manifold 220. Other components,such as disposable sorbent cartridges 210, volumetric pumps 201, 207,214 and 218, and dialyzer 202, are outside of the manifold.

FIG. 3 provides another perspective view of the compact manifold 300,with the thermal flow meter of the present invention integrated therein.As is shown in FIG. 3, the thermal flow meter 301 is placed at the inletport 311 to the dialyzer 310. The complete blood and dialysate flowpaths 302 of the hemodialysis/hemofiltration system are also molded intothe manifold 300. Besides the thermal flow meter 301, other functionalelements 303 of the blood purification system, as described above, arealso integrated into the compact manifold. One of ordinary skill in theart would appreciate that the number and location of the thermal flowmeter(s) that are integrated within the manifold may be varied accordingto the requirement and application of the blood purification system.Further, the thermal flow measurement device of the present inventionmay be used for any kind of fluid during dialysis, such as blood,dialysate, infusate, medications, etc. Finally, it should be appreciatedthat the description of the blood and dialysate circuits are for contextpurposes and should not be viewed as limiting to the nature, operation,or placement of the thermal flow meters of the present invention.

FIG. 4 illustrates the thermal fluid flow measurement device 401 of thepresent invention installed with the manifold 402 in the dialysismachine 410. As mentioned earlier, the manifold 402 has fluid flow pathsor tubing circuit 403 embedded within. The dialysis machine 410 has afront door 420 which can be opened to install the disposable manifold402. Further, the front door 420 is equipped with pins 421 that, whenthe door 420 is closed, can make contact with electrical points on themanifold 402 to read information or provide electrical input.

The thermal fluid flow measurement device 401 further comprises a seriesof contacts 411, 412 and 413. Operationally, as fluid (such as blood,dialysate or other fluids) flows during dialysis through the fluid flowpath 403, it passes the first contact 411 which is embedded in theplastic pathway. The contact 411 makes electrical contact with anelectrical source, which in one embodiment is a pin 421 on the machinefront door 420. The electrical source or pin is controlled by acontroller (not shown) in the dialysis machine 410. The electricalsource provides an electrical stimulus to the contact 411, which acts tomicro heat the contact based on a sine-wave method. In one embodiment,the micro heating process effectuates a temperature increase between 0.1and 1.0 degrees Celsius in the fluid being measured. This is effectuatedby means of micro heaters located at the first contact 411, whichproduce heat on receiving the electrical stimulus. Micro heaters for thethermal fluid flow measurement device of the present invention can bemanufactured using any design suitable for the application. In oneembodiment for example, the micro heater is made up of 10 turns of 30 gcopper wire wound around a pin located at the first contact position411.

As the contact 411 gets micro-heated, the resulting thermal energy actsto create a thermal wave, which propagates downstream from the firstcontact 411. A plurality of contacts, which in one embodiment are two innumber—412 and 413 are located downstream from the first contact 411,and are used to measure the time of flight of the thermal wave. Themeasured phase of the wave is then compared with the initial wavegenerated by the first contact 411. The phase difference thus determinedprovides an indication of the flow rate.

FIGS. 5 a through 5 c illustrate one embodiment of a flow cell withprobes that can be used for flow measurement. Referring to FIG. 5 a, atop view of one embodiment of the thermal flow meter 500 a of thepresent invention is shown. A channel 501 a encompasses a volume 502 athrough which fluid, such as water or saline solution (0.9 N) 503 aflows. In one embodiment, the channel has a height in the range of 1 mmto 5 mm (preferably 3 mm), a width in the range of 3 mm to 13 mm(preferably 8 mm), a length in the range of 10 mm to 100 mm (preferably50 mm), a channel area in the range of 3 mm² to 65 mm² (preferably 24mm²), and/or a a hydraulic diameter in the range of 1.5 mm to 7.22 mm(preferably 4.36 mm).

The direction of the fluid flow is shown by arrow 504 a. An excitationprobe 505 a is positioned proximate to a receiver probe 506 b. Thedistance the probes is an important feature of design, as the excitationfrequency at which the electrical stimulus needs to be delivered by theexcitation pin or probe 505 a depends on the spacing between the probes505 a and 505 b. In one embodiment, the excitation probe and receiverprobe are positioned less than 2 inch, preferably less than 0.8 inches,and more preferably approximately 0.6 inches, or approximately 15 mm,from each other. In this embodiment, excitation and measurement onlyrequires two contacts, each contact having a contact surface 507 a. Oneof ordinary skill in the art would appreciate that, in such a case, onlytwo contact points would be required, rather than three, as shown aboverelative to a disposable manifold and dialysis machine.

An excitation pin or probe 505 a is embedded in the channel 501 a andacts to provide a thermal stimulus (in the form of a thermal wave) tothe flowing fluid, which is then sensed and measured by the receivingcontact 506 a. In one embodiment, the body diameter of the pin or probeis in the range of 0.03 inches to 0.15 inches (preferably 0.08 inches),the diameter of the top contact surface is in the range of 0.025 inchesto 0.2 inches (preferably 0.125 inches), and is made of gold platedbrass or any other material having a density of approximately 8500kg/m³, a thermal conductivity of approximately 1.09 W/mK and/or aspecific heat of approximately 0.38 J/KgK.

In one embodiment, the bodies of both the excitation pin or probe 505 aand the receiving pin or probe 506 a are molded into the manifold (suchthat the pin or probe is not physical contact with the fluid and its topcontact area is exposed to one surface of the manifold). The body of thepin or probe is centered in the cell and fluid passes by it. The top ofthe pin is exposed so a spring loaded contact, from the instrumentpanel, can make thermal contact, thereby enabling the transfer ofthermal energy between the spring loaded contact and the contact surfaceof the pin.

For example, referring to FIG. 5 b, a side view of one embodiment of thethermal flow meter 500 b of the present invention is shown with thecontact surface 507 b exposed so that a spring loaded contact from theinstrument panel of the dialysis machine (shown in FIG. 4) can makethermal contact and thermal energy can be exchanged between the springloaded contact and the excitation pin or probe 505 b. A channel 501 bencompasses a volume 502 b through which fluid 503 b flows. Thedirection of the fluid flow is shown by arrow 504 b. An excitation probe505 b is positioned proximate to a receiver probe 506 b, each of whichhas a contact surface 507 b.

FIG. 5 c shows thermal flow meter 500 c from the end of the flow channel501 c, which contains a volume 502 c through which fluid 503 c flows.Here, only the receiver probe 506 c and its contact surface 507 c isshown. In one embodiment, the receiving contact or pin 506 c has astructure similar to that of the excitation pin 505 c and its top 507 cis also exposed. In one embodiment, the receiver pin surface 507 c isalso designed as a low thermal mass spring loaded contact. Theexcitation 505 a as well as receiver 505 a probes or pins are made up ofa suitable material which has high thermal and electrical conductivity,which in one embodiment is gold plated brass.

In one embodiment, a low thermal mass spring loaded contact in theinstrument, such as a dialysis machine, is temperature controlled usinga heater and a thermistor. The temperature control function thengenerates a cosine temperature wave form in the probe which isreflective of the temperature wave created in the spring loaded contact.The resultant excitation signal characteristic of the excitation pin maybe defined as:

e _(s) =E _(s) cos(ωt), where ωt is the excitation frequency.

The thermal response of the receiver pin may be characterized by thefollowing equation:

r _(r) =R _(r) sin(ωt+θ), where ωt is the excitation frequency and θ isthe phase.

One representation of the propagation of a thermal wave is shown inFIGS. 6 a and 5 b. Referring to FIG. 6 a, the arrow 601 represents thedirection of flow of fluid (and hence the direction of propagation of athermal wave) in a fluid pathway 602 in a channel. Measurement contactsare represented by 611, 612 and 613. Since the micro heater (not shown)is located proximate to the first contact 611, the thermal waveoriginates at the first contact, and then propagates towards the secondand third contacts 612 and 613 respectively, which are locateddownstream from the first contact 611. The distance between the second612 and third 613 contacts is 615.

FIG. 6 b illustrates exemplary wave measurements at the three contacts611, 612 and 613 of FIG. 6 a. Referring to FIGS. 6 a and 6 b, thethermal wave generated at the first contact 611 is represented by thefirst curve 621. Given that the flow is from left to right, this thermalwave will reach contact 612 at the second location slightly ahead of thetime than when it reaches the contact 613 at the third location. Theoutputs of the second and third contacts 612 and 613 are represented bythe curves 622 and 623, respectively.

The phase shift between the second 622 and third 623 signals can bemeasured by comparing the points of the zero crossing for each. Thedistance 615 between the second 612 and third 613 contacts divided bythe time between the respective zero crossings (also called time offlight) is equal to the flow velocity of the fluid. Further, multiplyingthe computed flow velocity by the diameter of the fluid pathway yieldsthe volume flow rate.

The thermal wave can be monitored by using temperature sensors, which inone embodiment are constructed of thermistors, such as Cantherm, partnumber, CWF4B153F3470, and are placed in physical contact with contactslocated at the second and third positions. In one embodiment, thecontacts are monitored/measured using thermal measuring devices (whichare in contact with the two metal contacts) in the dialysis machineitself. This eliminates the need for separate temperature measuringdevices to be integrated in the manifold. It should be appreciated that,in a preferred embodiment, a dialysis machine, or non-disposableinstrument, contains a processor and a memory which record a) theexcitation frequency communicated to the spring loaded contact which,upon installation of a disposable manifold, physically communicates withthe contact surface of the excitation probe and b) the frequency of thetemperature wave sensed by the receiver probe and communicated, throughthe contact surface of the receiver probe, to a spring loaded contact inthe dialysis machine, or non-disposable instrument. The processorimplements the derivations, described herein, to determine thetemperature levels and changes based upon the above-listed stored data.It should be further appreciated that this temperature information isthen communicated to a display driver which causes the information to bevisually displayed, or audibly communicated, via a user interface.

In one embodiment, the detection circuit examines the phase shift bymixing the excitation signal and receiver signal, performing acomparison, and subjecting the result to a low pass filter in order toget the phase shift information. More specifically, in one embodiment,phase detection is accomplished by multiplying the excitation frequencyby the receiver signal. The results yield a signal with two components,one at twice the frequency and one being a DC signal proportional to thephase shift between the excitation reference signal and the receiversignal. This is represented by the following equation:

${{Phase}\mspace{14mu} {Detection}\text{:}\mspace{14mu} e_{s}r_{r}} = {\frac{E_{s}R_{r}}{2}\left\lbrack {{\sin \left( {{2\omega \; t} + \theta} \right)} + {\sin \; \theta}} \right\rbrack}$

Where e_(s) is the excitation signal, r_(r) is the receiver signal, ωtis the excitation frequency and θ is the phase.

As described above, the present invention relies on a wave for time offlight measurement and not a thermal pulse. This method offers asignificant advantage because a thermal pulse disperses, resulting inuncertainty over where the pulse edge begins, and substantiallyincreases the measurement noise. Waves disperse as well but the phaseshifts of a sine wave, even after dispersion, remain more distinct.Therefore relying on sine wave for measurement introduces less noise.

Another advantage of the present invention lies in integrating thethermal flow rate sensor in the disposable manifold. The plastic used inthe manifold acts as a thermal insulator, which beneficially affectsmeasurements. As mentioned previously, in one embodiment spring-loadedprobes are used for the thermal flow measurement device, which makes itlow cost and disposable.

The design of the device of present invention is optimized in accordancewith three parameters: a) thermal excitation (frequency of the thermalinput signal), b) the expected flow rate (a slower flow rate requires adifferent frequency than a higher flow rate because a slower flow rateexperiences dispersion more), and c) amount and extent of thermaldispersion. In one embodiment, in order to minimize noise and improvedetection accuracy, one can set a key parameter as being constant, e.g.constant phase shift, constant frequency, or constant flow area.

In one embodiment, the constant phase shift method is implemented byusing a phase sensitive detector and a digitally controlled frequencygenerator. As described above, the time of flight causes a physicaldelay between the excitation probe and the receiver probe. At high flowrates the physical delay is small, while at low flow rates, the physicaldelay is large. Therefore, in order to maintain a constant phase shiftthe excitation frequency is controlled via feedback from the phasesensitive detector. A feedback loop is included in the system so thatimportant parameters such as excitation frequency can be dynamicallyadjusted such that the phase shift remains constant.

Referring to FIG. 11, a schematic of one embodiment of the presentinvention employing a constant phase shift mode of operation is shown.Liquid 1103 flowing through a channel 1101 passes by excitation probe1105 and receiver probe 1107, which are separated by a distance 1109, asdescribed above. In one embodiment, the channel 1101 is part of amanifold which is designed to be inserted into, and used within, adialysis machine. Once installed within the dialysis machine, thecontact surface of the excitation probe 1105 is made to thermallycontact a heater driver 1125 and the contact surface of the receiverprobe 1130 is made to thermally contact a temperature sensor 1130. Theheater driver 1125 and temperature sensor 1130 are in electrical contactwith a circuit, embodied in and/or integrated within, the dialysismachine.

On the excitation probe side, the circuit comprises a reference signalsource 1110 which transmits a signal having a phase θr to a summationdevice 1115, which also receives a signal input θm from a low passfilter, as described below. The two signals are summed, processed, orotherwise compared to yield an output which is transmitted to a voltagecontrolled oscillator 1120. The voltage controlled oscillator 1120outputs a signal, Rp where Rp=Kp sin(ωt), that is received by a heaterdriver 1125 and used to drive the heater driver 1125 to yield theexcitation wave which is thermally communicated to probe 1105.

The thermal wave propagates through the channel 1101 as a function ofthe fluid 1103 flow rate. The receiver probe 1107 which thermallycommunicates the sensed thermal wave to the temperature sensor 1130. Thethermal sensed wave can be expressed as a function as follows: Es=Kssin(ωt+θc).

As stated above, the temperature sensor 1130 is in electrical contactwith a circuit embodied within, or integrated into, the dialysismachine. The sensed thermal wave (Es) is communicated to a synchronousphase sensitive detector employing a multiplier component 1135, whichmultiplies the sensed thermal wave (Es) with an input signal from thevoltage controlled oscillator 1120 (Rn, where Rn=Kn cos(ωt)), yieldingan output signal EsRn. Output signal EsRn (which can be expressed asEsRn=(KnKs/2)[sin(2ωt+θc)+sin(θc)]) is input into the amplifier 1140 andamplified by constant K1. The amplified signal is then input into a lowpass filter 1145, which receives an input signal from the voltagecontrolled oscillator 1120. The input signal from the voltage controlledoscillator 1120 is used to vary the filter threshold, or cutoff, of thelow pass filter 1145. The output from the low pass filter 1145 (θm whichcan be expressed as a function of KnKsK1θc/2) is a signal that isindicative of the flow rate of the fluid, which can be derived by anymeans known to persons of ordinary skill in the art, and is communicatedback to said summation device 1115 for use in generating the referencesignal from the voltage controlled oscillator 1120.

FIG. 7 a is a table which illustrates the range of excitation frequencythat is dynamically adjusted to maintain a constant phase shift.Referring to FIG. 7, the determination process takes into account thevalues of various parameters such as flow rate 701, which varies between25 to 600 ml/min and flow velocity 702 which ranges from 17.36 mm/s to416.67 mm/s. Using a 15 mm value for probe separation 703, theexcitation frequency 705 will vary from ˜1.16 Hz@25 mL/min flow rate to27.78 Hz@ 600 mL/min flow rate. The corresponding values of travel timeand receiver amplitude are detailed in rows 704 and 706, respectively.Note that receiver amplitude is maintained at zero for a constant phaseshift.

FIG. 7 b illustrates the output of the phase sensitive detector plottedagainst time axis 710. The various curves 720 represent a series ofoutputs of the phase sensitive detector for different values of flowrate. The graphs in FIG. 7 b have been plotted for the values given inthe table of FIG. 7 a; accordingly, the flow rate ranges from 25 to 600ml/min and the corresponding excitation frequency varies from ˜1.16 Hzto 27.78 Hz.

In another embodiment, phase shift may be allowed to vary while thefrequency excitation remains constant. Constant frequency excitation isemployed along with a phase sensitive detector, while a feedbackmechanism is not used. FIG. 8 a illustrates a table detailing values ofvarious parameters when the excitation frequency 806 is maintained at1.157 Hz. This value is for flow rate 801 varying between 25 to 600ml/min and flow velocity 802 ranging from 17.36 mm/s to 416.67 mm/s.While the probe separation 803 is set at 15 mm, the corresponding valuesof travel time 804 range from 0.0360 sec (for Harmonic 805 value of1.000) to 0.864 sec. Varying phase shift is reflected in thecorresponding receiver amplitude values detailed in row 806. FIGS. 8 band 8 c illustrate two sets of outputs (for the range of flow ratesspecified in FIG. 8 a) of the phase sensitive detector plotted againsttime axis.

Referring to FIG. 12, a schematic of one embodiment of the presentinvention employing a constant frequency mode of operation is shown.Liquid 1203 flowing through a channel 1201 passes by excitation probe1205 and receiver probe 1207, which are separated by a distance 1209, asdescribed above. In one embodiment, the channel 1201 is part of amanifold which is designed to be inserted into, and used within, adialysis machine. Once installed within the dialysis machine, thecontact surface of the excitation probe 1205 is made to thermallycontact a heater driver 1225 and the contact surface of the receiverprobe 1230 is made to thermally contact a temperature sensor 1230. Theheater driver 1225 and temperature sensor 1230 are in electrical contactwith a circuit, embodied in and/or integrated within, the dialysismachine.

On the excitation probe side, the circuit comprises a reference signalsource 1210, such as a sine generator, which transmits a signal having afrequency (e.g. at or about 1.17 Hz) to a heater driver 1225. The sinegenerator 1210 outputs a signal, Rp where Rp=Kp sin(ωt), that isreceived by a heater driver 1225 and used to drive the heater driver1225 to yield the excitation wave which is thermally communicated toprobe 1205. It is preferred that the excitation frequency is low enoughso at low flow rates the phase shift is less than 80 degrees. The sinegenerator 1210 also outputs a signal, Rn where Rn=Kn cos(ωt), that isreceived by a multiplier 1235 and low pass filter 1245, as furtherdescribed below.

The thermal wave propagates through the channel 1201 as a function ofthe fluid 1203 flow rate. The receiver probe 1207 which thermallycommunicates the sensed thermal wave to the temperature sensor 1230. Thethermal sensed wave can be expressed as a function as follows: Es=Kssin(ωt+θc). The temperature sensor 1230 is in electrical contact with acircuit embodied within, or integrated into, the dialysis machine. Thesensed thermal wave (Es) is communicated to a synchronous phasesensitive detector employing a multiplier component 1235, whichmultiplies the sensed thermal wave (Es) with an input signal from thesine generator 1210 (Rn, where Rn=Kn cos(ωt)), yielding an output signalEsRn. Output signal EsRn (which can be expressed as EsRn=(KnKs/2)[sin(2wt+θc)+sin(θc)]) is input into the amplifier 1240 and amplified byconstant K1. The amplified signal is then input into a low pass filter1245, which receives an input signal from the sine generator 1210. Theinput signal from the sine generator 1210 is used to vary the filterthreshold, or cutoff, of the low pass filter 1245. The output from thelow pass filter 1245 (θm which can be expressed as a function ofKnKsK1θc/2) is a signal that is indicative of the flow rate of thefluid, which can be derived by any means known to persons of ordinaryskill in the art. It should be appreciated that the frequency cutoff ofthe low pass filter is approximately 1/20 of the frequency of theexcitation frequency. The low pass filter should attenuate the 2ωtsignal by at least 80 db.

FIG. 13 shows the relative phase shifts of signals generated in theconstant frequency mode with a low flow rate and a high flow rate. Anexcitation signal 1330 is generated at time 0. In a low flow ratescenario, the sensed signal 1320 is offset from the excitation signal1330 by a phase shift of θ_(LF) 1340 while, in a high flow ratescenario, the sensed signal 1310 is offset from the excitation signal1330 by a phase shift of θ_(hF) 1350.

Regardless of whether constant or varying phase shift method is employedfor measurement, using phase shift as the basis of flow measurement isadvantageous as compared to using amplitude, since amplitude can getaffected by external factors such as external temperature influences,which should not affect the phase shift.

In one embodiment, the non-invasive thermal fluid flow meter of thepresent invention provides a measurement range of 20 mL/min to 600mL/min. Besides the factors listed previously, other factors that areimportant for designing the thermal flow meter for optimum performanceinclude flow characteristics such as flow regime, maximum Reynoldsnumber and flow velocity; and physical characteristics of the flow cell,such as channel height, width and length.

FIG. 9 comprises a a table delineating an exemplary set of designparameters optimized such that the flow regime is kept laminar andReynold's number 909 is maintained under 2000, for a maximum flow rate901 of 600 ml/min. For keeping the flow regime laminar, channelsize—including channel height 902, width 903, length 904, area 905 andhydraulic diameter 906 are optimized. Reynold's number 909 is computedafter taking into account values of flow velocity 907, hydraulicdiameter 906 and properties of water 908, such as density, dynamicviscosity and kinematic viscosity.

In one embodiment, the flow cell is designed for turbulent flow regimeinstead of laminar. Such a design of the flow cell entails a constantflow area, which in turn would involve the flow area being widenedaround the probes (which is reduced around the probes for laminar flow).When the area at the probes widens, the fluid increases in velocityaround the probes and the increased velocity causes the flow regime tomove into the turbulent regime.

FIG. 10 is a table illustrating another set of exemplary designparameters for the excitation and receiver probes, which in oneembodiment are sized to have a thermal time constant 1005 under 1millisecond for optimum performance. The factors taken into account forthis purpose are the material—which in this case is brass, and itsproperties 1001 such as density, thermal conductivity and specific heat,as well as convection coefficient 1004. Accordingly the size 1002 andexposed surface area 1003 of the probes is determined.

Hereinbefore has been disclosed a system and method of non-invasivelymeasuring the rate of flow of fluid passing through a passageway using aphoto-acoustic flow meter of the present invention. It will beunderstood that various changes in the details, arrangement of elementsand operating conditions which have been herein described andillustrated in order to explain the nature of the invention may be madeby those skilled in the art without departing from the principles andscope of the invention. Therefore, the present examples and embodimentsare to be considered as illustrative and not restrictive, and theinvention may be modified within the scope of the appended claims.

1. A flow rate sensor for sensing the flow rate of a fluid passingthrough a channel of a disposable manifold that is installed in adialysis machine, comprising: An excitation probe having a body and acontact surface, wherein said excitation probe is located within saiddisposable manifold, wherein at least part of said excitation probe isphysically positioned within said channel, and wherein the excitationprobe generates a wave within said fluid in response to a first signal;A receiver probe having a body and a contact surface, wherein saidreceiver probe is located within said disposable manifold, wherein atleast part of said receiver probe is physically positioned within saidchannel, and wherein said receiver probe senses a wave within saidfluid; A heat source in said dialysis machine, wherein said heat sourcecomprises a contact surface that is on a surface of said dialysismachine and is configured to engage with said excitation probe only whensaid portion of said dialysis machine is placed in physical contact withsaid disposable manifold; and A temperature sensor in said dialysismachine, wherein said temperature sensor comprises a contact surfacethat is on the surface of the portion of said dialysis machine, whereinsaid temperature sensor is configured to thermally engage with saidreceiver probe only when said portion of said dialysis machine is placedin physical contact with said disposable manifold, and wherein saidtemperature sensor generates a second signal.
 2. The flow rate sensor ofclaim 1 wherein said heat source generates said first signal.
 3. Theflow rate sensor of claim 1 wherein said receiver probe generates asignal in response to sensing said wave within said fluid.
 4. The flowrate sensor of claim 2 wherein temperature sensor generates said secondsignal in response to the signal generated by said receiver probe inresponse to sensing said wave within said fluid.
 5. The flow rate sensorof claim 1 further comprising a reference signal generator, wherein saidreference signal generator outputs a reference signal.
 6. The flow ratesensor of claim 5 wherein said heat source receives said referencesignal from said reference signal generator and generates the firstsignal having a frequency derived from said reference signal.
 7. Theflow rate sensor of claim 6 further comprising a multiplier forreceiving an input signal from said reference signal generator, forreceiving said second signal and for outputting a third signal.
 8. Theflow rate sensor of claim 7 further comprising a filter for receiving afourth signal, wherein said fourth signal is a function of the thirdsignal, and for receiving an input signal from said reference signalgenerator.
 9. The flow rate sensor of claim 8 wherein the filter is alow pass filter.
 10. The flow rate sensor of claim 9 wherein the lowpass filter modulates its cutoff frequency based upon the input signalfrom said reference signal generator.
 11. The flow rate sensor of claim8 further comprising an amplifier for amplifying said third signal andgenerating said fourth signal.
 12. The flow rate sensor of claim 8wherein the low pass filter generates a filtered signal and wherein thereference signal generator generates said reference signal based, atleast in part, on said filtered signal.
 13. The flow rate sensor ofclaim 8 wherein said flow rate sensor dynamically adjusts said referencesignal in order to maintain a constant phase or a constant frequency.14. The flow rate sensor of claim 1 wherein said receiver probe isseparated from said excitation probe by a distance of less than twoinches.
 15. The flow rate sensor of claim 1 wherein said channel has anarea and wherein said area is in a range of 3 mm² to 65 mm².
 16. Theflow rate sensor of claim 1 wherein at least one of said receiver probeor excitation probe has a body having a diameter in the range of 0.03inches to 0.15 inches.
 17. The flow rate sensor of claim 1 wherein atleast one of the contact surfaces of said receiver probe or excitationprobe has a diameter in the range of 0.025 inches to 0.2 inches.
 18. Theflow rate sensor of claim 1 wherein the excitation probe and receiverprobe are embedded into a manifold and wherein the contact surfaces ofsaid receiver probe or excitation probe are externally exposed.
 19. Theflow rate sensor of claim 1 wherein the flow rate sensor has anoperative sensing range between 20 mL/min to 600 mL/min.
 20. The flowrate sensor of claim 19 wherein said flow rate sensor dynamicallyadjusts a reference signal in order to maintain a constant phase.